title: The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer.
abstract: BACKGROUND
  Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied.
  
  
  METHODS
  The impact of ER over-expression or down-expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERβ agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated by Western blot analysis.
  
  
  RESULTS
  PPARγ protein and activity were reduced by the over-expression of either ERα or ERβ, whereas repression of ERα or ERβ increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERβ activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERβ and PPARγ enhanced the expression of proapoptotic molecules, such as caspase-3 and apoptosis-inducing factor.
  
  
  CONCLUSIONS
  This study provides evidence supporting a cross-talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERβ significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Ryan
authors.initials: R
authors.lastname: Chu
authors.forename: Andrew
authors.initials: A
authors.lastname: van Hasselt
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Vlantis
authors.forename: Enders K W
authors.initials: EK
authors.lastname: Ng
authors.forename: Shirley Y W
authors.initials: SY
authors.lastname: Liu
authors.forename: Michael Dahua
authors.initials: MD
authors.lastname: Fan
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Ng
authors.forename: Amy B W
authors.initials: AB
authors.lastname: Chan
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Liu
authors.forename: Xin-ying
authors.initials: XY
authors.lastname: Li
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D047495:PPAR gamma / Q000096:biosynthesis / Q000378:metabolism*; D020239:Receptor Cross-Talk; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: apoptosis; estrogen receptors; peroxisome proliferator-activated receptor gamma; rosiglitazone; thyroid cancer